tip regimen combined with triplizumab neoadjuvant therapy for locally advanced penile cancer

Conditions: Penile Cancer

Summary: primary objective: to evaluate the efficacy and safety of tip (paclitaxel + ifosfamide + cisplatin) combined with toripalimab as a neoadjuvant treatment in locally advanced penile cancer

penile cancer is a rare malignant tumor, which often occurs in the inner plate of the prepuce and glans. squamous cell carcinoma is the most common pathological type. lymph node metastasis is a crucial factor that leads to poor prognosis of penile cancer. the 5-year os of penile cancer patients without lymph node metastasis is 90%. still, it goes down sharply in patients with inguinal lymph node metastasis and pelvic lymph node metastasis, which is 50% and 0%, respectively. using neoadjuvant chemotherapy to treat patients with locally advanced penile cancer (t4, any n stage, or any t stage, n3) may improve their prognosis. tip (paclitaxel + ifosfamide + cisplatin) regimen is the first-line neoadjuvant treatment recommended by nccn guidelines. pd-1 is an immune checkpoint molecule on the surface of t cells. in recent years, immune checkpoint inhibitors targeting pd-1 have shown good efficacy in a variety of tumors. some phase ii / iii clinical trials have shown that pd-1 inhibitors can improve the prognosis of patients with lung squamous cell carcinoma, head and neck squamous cell carcinoma, and cervical cancer. previous studies have found that pd-l1 is highly expressed in 40% - 60% of penile cancer, suggesting that penile cancer patients may benefit from immunotherapy. the management of penile cancer with lymph node metastasis is difficult, especially for the n2-3 stage. this phase ii study aims to explore an effective combination therapy for locally advanced penile cancer. 25 patients need to be enrolled.tip \& toripalimab will be administered every 21 days until surgery, evidence of disease progression, or onset of unacceptable toxicity.

Eligibility criteria:
inclusion criteria: 1. squamous cell carcinoma confirmed by histology or cytology; 2. clinical stage is locally advanced penile cancer (t4, any n stage; or any t stage, n3); 3. no prior chemotherapy for newly diagnosed or relapsed patients or the time from the last chemotherapy to relapse should be longer than 12 months; 4. there is at least one measurable lesion according to the solid tumor efficacy evaluation standard recist1.1; 5. the eastern cooperative oncology group (ecog) scored 0-2; 6. blood marrow function: hemoglobin(hb) \>/= 80g/l; white blood cell count \>/= 3.0x10\^9/l; neutrophil count \>/= 1.5x10\^9/l; platelet count \>/ = 100x10\^9/l; 7. liver function: ast, alt, alp \</= 2.5 uln; total bilirubin \</= 1.5 uln; 8. estimated survival \>/= 12 months; 9. no prior serious disease history of a systemic organ; 10. the participant understands this study procedure and signs the informed consent. exclusion criteria: 1. peripheral neuropathy degree \>/=2 (affecting patient's function); 2. previously received any other experimental drug treatment within 4 weeks before enrollment; 3. patients with other cancer at present, or have other malignant tumor histories within the past 5 years. except for (1) cured skin non-malignant melanoma; (2) curable tumor, including low-risk prostate cancer (t1a, gleason score\<6, psa\<0.5ng/ml), superficial bladder cancer and so on; (3) other solid tumors have received radical treatment, and no recurrence or metastasis has been found at least 5 years; 4. other serious or poorly controlled concomitant diseases, including but not limited to (1) severe or acute attack disease history of cardiovascular, liver, respiratory, kidney, blood, endocrine or neuropsychiatric system within 6 months; (2) active infection history and needed antibiotic treatment within 2 weeks before enrollment; (3) congestive heart failure (grade iii-iv); (4) unstable angina pectoris or myocardial infarction history within 6 months